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Hepatocellular carcinoma (HCC) is characterized by high incidence, significant mortality, and marked heterogeneity, making accurate molecular subtyping essential for effective treatment. Using multi-omics data from HCC patients, we applied diverse clustering algorithms to identify three HCC subtypes (HSs) with distinct prognostic characteristics. Among these, HS1 emerged as an immune-compromised subtype associated with the poorest prognosis. Additionally, we developed a novel, robust, and highly accurate machine learning-guided prognostic signature (MLPS) by integrating multiple machine learning algorithms and their combinations. Our study also identified SLC2A1, the core gene of MLPS, as being highly expressed during advanced stages of tumor progression. Knockdown experiments demonstrated that reducing SLC2A1 expression significantly suppressed the malignant behavior of HCC cells. Furthermore, SLC2A1 expression was linked to responsiveness to dasatinib and vincristine, suggesting potential therapeutic relevance. MLPS and SLC2A1 offer promising tools for individualized prognosis prediction and targeted therapy in HCC, providing new opportunities to improve patient outcomes.

Maize is one of the most important crops for human food, animal feed, and industrial raw materials. Ear shank length (ESL) and ear shank node number (ESNN) are crucial selection criteria in maize breeding, impacting grain yield and dehydration rate during mechanical harvesting. To unravel the genetic basis of ESL and ESNN in maize, an association panel consisting of 379 multi-parent doubled-haploid (DH) lines was developed for genome-wide association studies (GWAS) and genomic selection (GS). The heritabilities of ESL and ESNN were 0.68 and 0.55, respectively, which were controlled by genetic factors and genotype-environment interaction factors. Using five different models for GWAS, 11 significant single nucleotide polymorphisms (SNPs) located on chromosomes 1, 2, and 4 were identified for ESL, with the phenotypic variation explained (PVE) value of each single SNP ranging from 4.91% to 21.35%, and 11 significant SNPs located on chromosomes 1, 2, 4, and 5 were identified for ESNN, with the PVE value of each SNP ranging from 1.22% to 18.42%. Genetic regions in bins 1.06, 2.06, and 2.08 were significantly enriched in SNPs associated with ear shank-related traits. The GS prediction accuracy using all markers by the five-fold cross-validation method for ESL and ESNN was 0.39 and 0.37, respectively, which was significantly improved by using only 500-1000 significant SNPs with the lowest P-values. The optimal training population size (TPS) and marker density (MD) for ear shank-related traits were 50%-60% and 3000, respectively. Our results provide new insights into the GS of ear shank-related traits.

The field of gene therapy using Adeno-associated viral (AAV) vector delivery is rapidly advancing in the biotherapeutics industry. Despite its successes, AAV manufacturing remains a challenge due to limited production yields. The triple plasmid transfection of HEK293 cells represents the most extensively utilized system for AAV production. The regulatory factors and mechanisms underlying viral production in HEK293 cells are largely unknown. In this study, we isolated high-titer AAV production clones from a parental HEK293 population using a single limiting dilution step, and subsequently elucidating their underlying molecular mechanisms through whole transcriptome analysis. LncRNA TCONS_00160397 was upregulated in clones and shown to promoted HEK293 cells proliferation and improved the titer of AAV production. Mechanistically, results from proteomics and metabolomics indicated that TCONS_00160397 regulated the ABC transporters pathway. These findings furnish a rich repository of knowledge and actionable targets for the rational optimization of HEK293-based producer lines, thereby paving the way for tangible improvements in AAV vector output and expediting the broad implementation of gene therapies.

The role of transforming growth factor-beta (TGF-β) is dual, such that, it inhibits tumor development in initial stage and promotes metastasis in later stage. The present study is aimed to analyse the relevance of different types of TGF-β and their receptors on the overall survival (OS) and TGF-β driven gene expression in individuals with cervical cancer (CC) using ONCODB and GEPIA databases. The in-silico gene expression analysis showed, TGF-β1 and TGFβR2 are upregulated in cells infected with human papilloma virus (HPV)16, whereas, TGF-β2, TGFβR1 and TGFβR3 expression were downregulated. In HPV 18 infected cells, TGF-β1, TGF-β2 and TGFβR1 were downregulated, meanwhile, TGF-β3, TGFβR2 and TGFβR3 were upregulated. OS analysis of CC patients with different TGF-β expression revealed that, TGF-β1, TGF-β2, TGF-β3 and TGFβR2 were associated with reduced survival rate. Further, we identified four microRNAs (miRNAs) (hsa-miR-21-5p, hsa-miR-29b-3p, hsa-miR-101-3p and hsa-miR-130a-3p) interacted favorably with TGF-β in HPV 16 and 18 positive samples using MIENTURNET. This present review further emphasizes that, targeting TGF-β could be a novel and futuristic approach for CC management and therapeutics.

Purpose: Long non-coding RNAs (lncRNAs) play important roles in progression of neuroblastoma (NB). LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to affect the development of multiple tumors. However, the effect of NEAT1 on NB remain unclear. In this study, the new mechanisms whereby how NEAT1 influences tumor progression in NB was investigated.

Methods: RT-qPCR, western blot, bioinformatics, cell growth, Transwell, and flow cytometric analyses were performed to determine how NEAT1 synchronously regulates the miR-873-5p/MYCN proto-oncogene(MYCN) and miR-873-5p/polypeptide N-acetylgalactosaminyltransferase 1(GalNAcT-I) axes to accelerate the progression of NB. NB-bearing animal models were established to evaluate the function of NEAT1 in NB. The relationships between transcription factor coactivatorassociated arginine methyltransferase 1 (CARM1) and NEAT1, NEAT1 and miR-873-5p, miR-873-5p and GalNacT-I or MYCN, were verified using luciferase reporter gene assay, respectively.

Results: Our study revealed elevated levels of NEAT1 expression in NB cells and tissues which was associated with an advanced pathological stage and poor prognostic outcomes. According to in vitro gain- and loss- of function experiments, NEAT1 enhances progression of NB. NEAT1 silencing was found to inhibit NB proliferation in vivo. Mechanistically, to achieve upstream regulation, epigenetic downregulation of NEAT1 was achieved via the inhibition of CARM1. NEAT1 was found to positively regulate MYCN and GalNAcT-I levels as a competitive sponge of miR-873-5p.

Conclusion: Activity of the lncRNA NEAT1 can be triggered via CARM1, which synchronously promotes NB development via the miR-873-5p/MYCN and miR-873-5p/GalNAcT-I axes. These findings shed light on the novel molecular mechanisms underlying NB progression.

The basic helix-loop-helix (bHLH) family, a prominent group of transcription factors, is involved in plant growth, development, and secondary metabolic processes. Petunia (Petunia hybrida), a beloved and widely cultivated garden flower, boasts a diverse array of varieties, some of which exude a captivating fragrance that has garnered immense popularity. The aromatic allure of petunias primarily stems from the presence of volatile benzenoids/phenylpropanoids, the principal floral scent compounds. But whether bHLH transcription factors regulate petunia floral scent compound synthesis is not clear. In this study, we sought to screen the putative candidate member of bHLH which can be involved in the biosynthesis of benzenoids/phenylpropanoids by examining 63 members of the petunia bHLH gene family. Phylogenetic analysis of the 63 petunia bHLH proteins them into 16 subgroups. Almost all bHLH members contained alkaline/helix-loop-helix domains. Based on the reported RNA sequencing data of P. hybrida 'Mitchell', 30 assembled sequences were mapped to the bHLH genes of P. axillaris. Further qRT-PCR assays suggested that PhbHLH19 might be the putative candidate member in the biosynthesis of benzenoids/phenylpropanoids. PhbHLH19 showed higher expression levels in the petal limb but was lowly expressed at the bud stage, with a rapid increase in the expression level when flowers opened. The expression of PhbHLH19 displayed a significant positive correlation with that of PhPAL2, and the yeast one-hybrid assay verified that PhbHLH19 can bind to the promoter of PhPAL2. Moreover, a dual-luciferase assay proved the transcriptional activation of PhbHLH19 on PhPAL2. These findings suggested that PhbHLH19 might be a putative candidate in the regulation of benzenoid/phenylpropanoid synthesis by activating PhPAL2 expression.

Gastric cancer (GC) has been ranked as the third incidence tumors globally. Long non-coding RNA (lncRNA) NRAV has been reported as a tumor-enhancer in the development of human cancers, whereas the function of NRAV in GC remains to be elucidated. The aim of this research was to explore the underlying function of NRAV in GC. Through comprehensive bioinformatics analysis, a significantly elevation of NRAV was found in both human GC tissues and cell lines, which indicated the poor prognosis of GC patients. Then, we conducted a series of functional experiments to illustrate the role of NRAV in GC. The results showed that the down-regulation of NRAV exhibited a significant inhibitory effect on GC cell proliferation and migration, while NRAV overexpression promoted GC cell proliferation and migration. Through xenograft mouse tumor model, the suppression of NRAV led to a reduction in the growth of tumor mice, whereas overexpression of NRAV notably enhanced tumor growth. Finally, EFHC1 was revealed as the potential target gene of NRAV. Overall, our findings indicated the promising application of NRAV as a therapeutic target and prognostic biomarker for GC.

Asthma is a complex disease characterized by reversible and intermittent airway obstruction that has shown a high prevalence and unacceptable mortality in adults. In recent years, several genome-wide association studies (GWAS) have identified variants linked to asthma susceptibility. The DAD1 gene is known for regulating programmed cell death, and OXA1L is described for its involvement in mitochondrial biogenesis and oxidative phosphorylation. The present study aimed to identify variants in the DAD1 and OXA1L genes and to evaluate the association with asthma and atopy markers in adults. 1,084 individuals were divided into mild to moderate asthma, severe asthma, and participants with no asthma (controls). Association analyses were performed using a multivariate logistic regression model adjusted for sex, age, body mass index (BMI), smoking, forced expiratory volume in 1 s (FEV1), and component ancestry master (PC1) using PLINK 1.9 software. This study identified new variants in the DAD1 and OXA1L genes that had never been described before. The C allele of rs200470407 in OXA1L was negatively associated with poor asthma control (OR: 0.32; p-value 0.049) and increased IL-13 (p-value < 0.0001). The alternative allele of rs1681577 was associated with severe asthma (OR: 2.23; p-value 0.01), pulmonary obstruction (OR: 4.12; p-value 0.046), and eosinophilia (OR: 2.42; p-value < 0.001). Our findings demonstrate that variants in the DAD1 and OXA1L genes are linked to asthma and atopy in Brazilian adults.

Improving egg quality and enhancing production efficiency are essential goals in poultry breeding. CDH5 encodes a cadherin involved in Ca²⁺ transport in endothelial cells. The role of CDH5 in regulating duck egg quality and its mechanisms affecting Ca²⁺ concentrations in duck uterine epithelial cells remains unclear. This study evaluated egg quality traits of the Putian black duck and conducted an association analysis with blood biochemical indices and single nucleotide polymorphisms in CDH5. Additionally, we constructed a CDH5 overexpression vector and synthesized specific siRNAs for transfection into Putian black duck uterine epithelial cells to assess Ca²⁺ concentrations. Our results revealed a significant association between egg quality and five novel SNPs in CDH5, along with various blood biochemical indices. Further experiments demonstrated that CDH5 overexpression and knockdown reduced Ca²⁺ concentrations in the uterine epithelial cells of Putian black ducks.

In recent years, the increase in extreme climates, such as persistent high temperatures and drought, has adversely affected the growth and development of fast-growing trees. Melatonin (MT) plays an important role in plant responses to biotic and abiotic stresses, yet there is a lack of research on the specific role of limiting enzyme genes for MT biosynthesis in fast-growing woody plants. In this study, we investigated the function of PtoASMT, a key rate-limiting enzyme encoding gene for MT biosynthesis, which can be induced by drought, salt, and the phytohormones ABA, SA and JA. Our results show that: (1) PtoASMT was widely expressed in all tissues of poplar, but was highly expressed in petioles, moderately expressed in roots, stems, shoots and young leaves, exhibiting a typical diurnal expression rhythm in leaves, with the encoded protein localized on chloroplasts; (2) the content of MT was significantly promoted in overexpressing PtoASMT transgenic poplar plants, but there were no obvious differences in their growth and development; (3) overexpressing PtoASMT plants exhibited stronger drought tolerance, accumulating less reactive oxygen species (ROS) under drought stress relative to wild-type plants, whereas knockout PtoASMT plants were more sensitive and accumulated more ROS; (4) overexpressing PtoASMT plants were more resistant to fungi Dothiorella gregaria than WT plants, while knockout plants showed higher sensitivity; meanwhile, the expression of disease resistance-related genes (PRs and JAZ10) was significantly altered. We conclude that PtoASMT enhances the resistance of poplar to drought and Dothiorella gregaria by mediating MT biosynthesis in poplar. These findings contribute to a better understanding the role of ASMT gene in MT accumulation and stress resistance in poplar.